Identifying neurodevelopmental anomalies of white matter microstructure associated with high risk for psychosis in 22q11.2DS

Article Article scientifique Article Identifying neurodevelopmental anomalies of white matter microstructure associated with high risk for psychosis in 22q11.2DS eng 2020 author Van Der Molen Joëlle Ismay Rosanne 849914 author Padula Maria 811907 author Zoeller Daniela 846743 author Sandini Corrado 0000-0003-2933-1607 846736 author Schneider Maude 594384 author Schaer Marie 0000-0001-8479-6365 510515 author Eliez Stéphan 0000-0002-8269-3028 39336 408 10.1038/s41398-020-01090-z 33235187 2158-3188 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686319/ Disruptions of white matter microstructure have been widely reported in schizophrenia. However, the emergence of these alterations during preclinical stages remains poorly understood. 22q11.2 Deletion Syndrome (22q11.2DS) represents a unique model to study the interplay of different risk factors that may impact neurodevelopment in premorbid psychosis. To identify the impact of genetic predisposition for psychosis on white matter development, we acquired longitudinal MRI data in 201 individuals (22q11.2DS = 101; controls = 100) aged 5-35 years with 1-3 time points and reconstructed 18 white matter tracts using TRACULA. Mixed model regression was used to characterize developmental trajectories of four diffusion measures-fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivity (MD) in each tract. To disentangle the impact of additional environmental and developmental risk factors on white matter maturation, we used a multivariate approach (partial least squares (PLS) correlation) in a subset of 39 individuals with 22q11.2DS. Results revealed no divergent white matter developmental trajectories in patients with 22q11.2DS compared to controls. However, 22q11.2DS showed consistently increased FA and reduced AD, RD, and MD in most white matter tracts. PLS correlation further revealed a significant white matter-clinical risk factors relationship. These results indicate that while age-related changes are preserved in 22q11.2DS, white matter microstructure is widely disrupted, suggesting that genetic high risk for psychosis involves early occurring neurodevelopmental insults. In addition, multivariate modeling showed that clinical risk factors further impact white matter development. Together, these findings suggest that genetic, developmental, and environmental risk factors may play a cumulative role in altering normative white matter development during premorbid stages of psychosis. Dewey 616.89 Dewey 616.0757 Dewey 150 Swiss National Science Foundation Swiss VCFS Cohort: a 10-year longitudinal investigation from genes to brain to cognition for understanding psychosis proneness in 22q11.2 deletion 144260 CH Projects Swiss National Science Foundation NCCR 'SYNAPSY - The synaptic bases of mental diseases' (phase III) 185897 CH Programmes Swiss National Science Foundation Measuring trajectories of cerebral development associated with autism in the first years of life 163859 CH Careers 60 Département de psychiatrie 225 62 Département de radiologie et informatique médicale 227 108 Section de psychologie 71 false 421 Laboratoire d'imagerie et de psychopathologie développementale 693 1284 NCCR Synapsy Translational Psychiatry 10 1 ae788f51-b905-429b-9022-ff486c319933 Article (Published version) Public Bagautdinova.pdf 4562182 application/pdf CC BY c0f940be-cf5f-4cbd-aef4-f45c4a3d4785 Supplemental data Public 41398_2020_1090_MOESM1_ESM.pdf 2594644 application/pdf openAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale Faculté de psychologie et des sciences de l'éducation / Section de psychologie

Title	Published in	Year	Views	Downloads

Identifying neurodevelopmental anomalies of white matter microstructure associated with high risk for psychosis in 22q11.2DS	Translational Psychiatry	2020	445	172
Aberrant white matter development in 22q11.2 Deletion Syndrome and association with risk factors of psychosis		2018	436	197

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Van Der Molen, Joëlle Ismay Rosanne